Endostatin, an antiangiogenic protein, is expressed in the unilateral ureteral obstruction mice model.
BACKGROUND
Extracellular matrix accumulation, epithelial-to-mesenchymal transition, tubular atrophy and loss of peritubular capillary network are hallmarks of tubulointerstitial injury in progressive renal diseases. In this study, we analyzed endostatin expression in kidneys subjected to unilateral ureteral obstruction (UUO).


METHODS
Collagen XVIII mRNA expression was evaluated by real-time polymerase chain reaction (PCR). Endostatin and CD31 protein levels were analyzed by Western blot and immunohistochemistry. In vitro quantification of collagen XVIII and fibrosis-related genes in HK2 cells was performed by real-time PCR.


RESULTS
UUO significantly increased collagen XVIII mRNA expression and released a 30-kDa endostatin fragment. Immunohistochemistry revealed endostatin expression increased in injured tissue, mainly on tubular cells. Of interest, expression of CD31 was significantly reduced by UUO. Endostatin administration in vitro did not modify the expression of genes related to fibrosis development. However, in vitro TGF-beta1 administration induced expression of collagen XVIII/endostatin mRNA in human tubular cells.


CONCLUSIONS
Endostatin is expressed during the progression of renal fibrosis in vitro and in vivo, suggesting a role for endostatin in development of tubulointerstitial injury.
Maciel
Thiago T
TT
Nephrology Division, Federal University of São Paulo, São Paulo - Brazil. thiagotrovati@uol.com.br
Coutinho
Enia L
EL
Soares
Debora
D
Achar
Edurardo
E
Schor
Nestor
N
Bellini
Maria H
MH
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D043170:Collagen Type XVIII / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D053773:Transforming Growth Factor beta1